In humans, gastrin is a hormone that stimulates secretion of gastric acid by the stomach. It is released by G cells in the stomach and duodenum.
The GAS gene is located on the long arm of the seventh chromosome (17q21).
Synthesis and release
Gastrin is a linear peptide hormone produced by G cells that are located mainly in the antrum of the stomach and the D cells of the pancreatic islets. It is secreted into the bloodstream. Gastrin is found primarily in three forms: gastrin-34 ("big gastrin"), gastrin-17 ("little gastrin"), and gastrin-14 ("minigastrin"). The numbers refer to the amino acid count.
Gastrin is released in response to certain stimuli. These include: stomach distension, vagal stimulation (mediated by the neurocrine bombesin, or GRP in the human), the presence of partially digested proteins especially amino acids and hypercalcemia. Gastrin release is inhibited by the presence of acid (primarily the secreted HCl) in the stomach (a case of negative feedback). Somatostatin also inhibits the release of gastrin, along with secretin, GIP, VIP, glucagon and calcitonin.
The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid. This is done either directly or indirectly:
- Directly: binds onto CCK-B receptors on parietal cells stimulating them to secrete H+ ions.
- Indirectly: binds onto CCK-B receptors on ECL cells in the stomach, which then responds by releasing histamine, which in turn acts in a paracrine manner on parietal cells stimulating them to secrete H+ ions.
It also causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin. Pepsinogen is converted to pepsin in a low pH environment, and the HCl provides a suitable environment for its activity. It can also increase antral muscle mobility and trophic effect on GI tract. Gastrin has also been shown to induce production of pancreatic enzymes by acinar cells.
Factors influencing secretion
- Stimulatory factors: dietary protein and amino acids, high blood calcium. (i.e. during the gastric phase)
- Inhibitory factor: acidity (pH below 3) - a negative feedback mechanism, exerted via the release of somatostatin from D cells in the stomach, which inhibits gastrin and histamine release.
- Stimulatory factor: bombesin
- Inhibitory factor: somatostatin - acts on somatostatin-2 receptors on G cells. in a paracrine manner via local diffusion in the intercellular spaces, but also systemically through its release into the local mucosal blood circulation; it inhibits acid secretion by acting on parietal cells.
- Stimulatory factors: Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP)
- Stimulatory factor: epinephrine
- Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin
Role in disease
In the Zollinger-Ellison syndrome, gastrin is produced at excessive levels, often by a gastrinoma (gastrin-producing tumor, mostly benign) of the antrum or the pancreas. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin test" can be performed.